Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis
The transcription factor NF-κB is a central mediator of inflammation with multiple links to thrombotic processes. In this review, we focus on the role of NF-κB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. All these cells expr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00085/full |
| _version_ | 1818533091279372288 |
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| author | Marion Mussbacher Manuel Salzmann Christine Brostjan Bastian Hoesel Christian Schoergenhofer Hannes Datler Philipp Hohensinner José Basílio Peter Petzelbauer Alice Assinger Johannes A. Schmid |
| author_facet | Marion Mussbacher Manuel Salzmann Christine Brostjan Bastian Hoesel Christian Schoergenhofer Hannes Datler Philipp Hohensinner José Basílio Peter Petzelbauer Alice Assinger Johannes A. Schmid |
| author_sort | Marion Mussbacher |
| collection | DOAJ |
| description | The transcription factor NF-κB is a central mediator of inflammation with multiple links to thrombotic processes. In this review, we focus on the role of NF-κB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. All these cells express NF-κB, which mediates important functions in cellular interactions, cell survival and differentiation, as well as expression of cytokines, chemokines, and coagulation factors. Even platelets, as anucleated cells, contain NF-κB family members and their corresponding signaling molecules, which are involved in platelet activation, as well as secondary feedback circuits. The response of endothelial cells to inflammation and NF-κB activation is characterized by the induction of adhesion molecules promoting binding and transmigration of leukocytes, while simultaneously increasing their thrombogenic potential. Paracrine signaling from endothelial cells activates NF-κB in vascular smooth muscle cells and causes a phenotypic switch to a “synthetic” state associated with a decrease in contractile proteins. Monocytes react to inflammatory situations with enforced expression of tissue factor and after differentiation to macrophages with altered polarization. Neutrophils respond with an extension of their life span—and upon full activation they can expel their DNA thereby forming so-called neutrophil extracellular traps (NETs), which exert antibacterial functions, but also induce a strong coagulatory response. This may cause formation of microthrombi that are important for the immobilization of pathogens, a process designated as immunothrombosis. However, deregulation of the complex cellular links between inflammation and thrombosis by unrestrained NET formation or the loss of the endothelial layer due to mechanical rupture or erosion can result in rapid activation and aggregation of platelets and the manifestation of thrombo-inflammatory diseases. Sepsis is an important example of such a disorder caused by a dysregulated host response to infection finally leading to severe coagulopathies. NF-κB is critically involved in these pathophysiological processes as it induces both inflammatory and thrombotic responses. |
| first_indexed | 2024-12-11T17:54:06Z |
| format | Article |
| id | doaj.art-f40eb3d312af4c839abff13746f15be5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T17:54:06Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f40eb3d312af4c839abff13746f15be52022-12-22T00:56:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00085401678Cell Type-Specific Roles of NF-κB Linking Inflammation and ThrombosisMarion Mussbacher0Manuel Salzmann1Christine Brostjan2Bastian Hoesel3Christian Schoergenhofer4Hannes Datler5Philipp Hohensinner6José Basílio7Peter Petzelbauer8Alice Assinger9Johannes A. Schmid10Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaDepartment of Surgery, General Hospital, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaSkin and Endothelial Research Division, Department of Dermatology, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, AustriaThe transcription factor NF-κB is a central mediator of inflammation with multiple links to thrombotic processes. In this review, we focus on the role of NF-κB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. All these cells express NF-κB, which mediates important functions in cellular interactions, cell survival and differentiation, as well as expression of cytokines, chemokines, and coagulation factors. Even platelets, as anucleated cells, contain NF-κB family members and their corresponding signaling molecules, which are involved in platelet activation, as well as secondary feedback circuits. The response of endothelial cells to inflammation and NF-κB activation is characterized by the induction of adhesion molecules promoting binding and transmigration of leukocytes, while simultaneously increasing their thrombogenic potential. Paracrine signaling from endothelial cells activates NF-κB in vascular smooth muscle cells and causes a phenotypic switch to a “synthetic” state associated with a decrease in contractile proteins. Monocytes react to inflammatory situations with enforced expression of tissue factor and after differentiation to macrophages with altered polarization. Neutrophils respond with an extension of their life span—and upon full activation they can expel their DNA thereby forming so-called neutrophil extracellular traps (NETs), which exert antibacterial functions, but also induce a strong coagulatory response. This may cause formation of microthrombi that are important for the immobilization of pathogens, a process designated as immunothrombosis. However, deregulation of the complex cellular links between inflammation and thrombosis by unrestrained NET formation or the loss of the endothelial layer due to mechanical rupture or erosion can result in rapid activation and aggregation of platelets and the manifestation of thrombo-inflammatory diseases. Sepsis is an important example of such a disorder caused by a dysregulated host response to infection finally leading to severe coagulopathies. NF-κB is critically involved in these pathophysiological processes as it induces both inflammatory and thrombotic responses.https://www.frontiersin.org/article/10.3389/fimmu.2019.00085/fullNF-kappa B signalinginflammationthrombosisvasculaturecoagulationsepsis |
| spellingShingle | Marion Mussbacher Manuel Salzmann Christine Brostjan Bastian Hoesel Christian Schoergenhofer Hannes Datler Philipp Hohensinner José Basílio Peter Petzelbauer Alice Assinger Johannes A. Schmid Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis Frontiers in Immunology NF-kappa B signaling inflammation thrombosis vasculature coagulation sepsis |
| title | Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis |
| title_full | Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis |
| title_fullStr | Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis |
| title_full_unstemmed | Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis |
| title_short | Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis |
| title_sort | cell type specific roles of nf κb linking inflammation and thrombosis |
| topic | NF-kappa B signaling inflammation thrombosis vasculature coagulation sepsis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00085/full |
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